1. Field of the Invention
This invention relates to a novel process for producing N-alkylhydroxylamines represented by the formula (I) EQU rnh-oh (i)
wherein R represents an alkyl group having 1 to 4 carbon atoms which may be substituted with at least one substituent, and to novel intermediates therefor.
2. Brief Description of the Prior Art
Hitherto, a wide variety of alkylhydroxylamines were known to be useful as starting materials and intermediates for producing various compounds. For example, 1-amino-3-hydroxylaminopropane is useful as an intermediate for the preparation of schizokinen which is known to be useful as a growth factor of fungi, and 2-amino-3-hydroxylaminopropionic acid is useful as a precursor for the synthesis of alanosine which is known to be useful as antiviral and antitumor agents. Further, 5-N-hydroxylornithine is useful as constituting a basic skeleton of rhodotorulic acid or ferrichrome. In general, most of the alkylhydroxylamines are important starting materials for the preparation of various pharmaceuticals, for example, ferrioxamines.
Typical conventional procedures for the preparation of alkylhydroxylamines include (1) a process comprising reduction of the corresponding nitro compound with zinc powder in the presence of ammonium chloride [W. Keller-Schierlein et al, Helv. Chim. Acta., 48, 710 (1965)], (2) a process comprising hydrolysis or hydrazinolysis of a nitron obtainable by the condensation of anti-benzaldoxime and an alkyl halide [C. N. Eaton et al, J. Med. Chem., 16, 289 (1973)], and (3) a process comprising reaction between an alkyl halide and hydroxylamine [G. C. Lanani, E. Lazzari and A. Diena, Farmaco, Ed. Sci., 24, 169 (1969)]. However, none of these conventional processes is advantageous in producing N-alkylhydroxylamines on an industrial scale. That is, in the conventional process (1) above, there are various problems in producing the necessary starting materials used in this process, i.e., nitro compounds, since silver nitrate must be used in producing these nitro compounds whereby the type of N-alkylhydroxylamines which are capable of being produced is markedly limited. In the conventional process (2) above, the anti-benzaldoxime used as a starting material is unstable and further only a DL-form of alkylhydroxylamines can be produced in this process since a strong alkali is used in the condensation of the alkyl halide and antibenzaldoxime. In the conventional process (3) above, side-reactions tend to occur thereby reducing the yield of the desired product and, therefore, this conventional process cannot be considered as an advantageous process for producing N-alkylhydroxylamines.